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PMID- 29287080
OWN - NLM
STAT- In-Data-Review
LR  - 20171229
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 12
DP  - 2017
TI  - Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced 
      liver injury (DILI) as biomarkers of recovery.
PG  - e0189436
LID - 10.1371/journal.pone.0189436 [doi]
AB  - BACKGROUND: There is a clear need for better biomarkers of
      drug-induced-liver-injury (DILI). AIMS: We aimed to evaluate the possible
      prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin 
      and alpha-2-macroglobulin, in patients with DILI. METHODS: We analyzed cases and 
      controls included in the IMI-SAFE-T-DILI European project, from which serum
      samples had been stored in a dedicated biobank. The analyses of ActiTest and
      FibroTest had been prospectively scheduled. The primary objective was to analyze 
      the performance (AUROC) of ActiTest components as predictors of recovery outcome 
      defined as an ALT <2x the upper limit of normal (ULN), and BILI <2x ULN. RESULTS:
      After adjudication, 154 patients were considered to have DILI and 22 were
      considered to have acute liver injury without DILI. A multivariate regression
      analysis (ActiTest-DILI patent pending) combining the ActiTest components without
      BILI and ALT (used as references), apolipoprotein-A1, haptoglobin,
      alpha-2-macroglobulin and GGT, age and gender, resulted in a significant
      prediction of recovery with 67.0% accuracy (77/115) and an AUROC of 0.724
      (P<0.001 vs. no prediction 0.500). Repeated apolipoprotein-A1 and haptoglobin
      remained significantly higher in the DILI cases that recovered (n = 65) versus
      those that did not (n = 16), at inclusion, at 4-8 weeks and at 8-12 weeks. The
      same results were observed after stratification on APAP cases and non-APAP cases.
      CONCLUSIONS: We identified that apolipoprotein-A1 and haptoglobin had significant
      predictive values for the prediction of recovery at 12 weeks in DILI, enabling
      the construction of a new prognostic panel, the DILI-ActiTest, which needs to be 
      independently validated.
FAU - Peta, Valentina
AU  - Peta V
AD  - Department of Research, Biopredictive, Paris, France.
FAU - Tse, Chantal
AU  - Tse C
AD  - Department of Biochemistry, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
FAU - Perazzo, Hugo
AU  - Perazzo H
AD  - Department of Hepatology, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
FAU - Munteanu, Mona
AU  - Munteanu M
AD  - Department of Research, Biopredictive, Paris, France.
FAU - Ngo, Yen
AU  - Ngo Y
AD  - Department of Research, Biopredictive, Paris, France.
FAU - Ngo, An
AU  - Ngo A
AD  - Department of Research, Biopredictive, Paris, France.
FAU - Ramanujam, Nittia
AU  - Ramanujam N
AD  - Department of Biochemistry, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
FAU - Verglas, Lea
AU  - Verglas L
AD  - Department of Biochemistry, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
FAU - Mallet, Maxime
AU  - Mallet M
AD  - Department of Hepatology, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
FAU - Ratziu, Vlad
AU  - Ratziu V
AD  - Department of Hepatology, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
AD  - University Pierre et Marie Curie, Institut National de la Sante et de la
      Recherche Medicale UMR 938, Paris, France.
FAU - Thabut, Dominique
AU  - Thabut D
AD  - Department of Hepatology, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
AD  - University Pierre et Marie Curie, Institut National de la Sante et de la
      Recherche Medicale UMR 938, Paris, France.
FAU - Rudler, Marika
AU  - Rudler M
AD  - Department of Hepatology, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
FAU - Thibault, Vincent
AU  - Thibault V
AD  - Department of Virology, Groupe Hospitalier Pitie-Salpetriere, Assistance Publique
      Hopitaux de Paris, Paris, France.
FAU - Schuppe-Koistinen, Ina
AU  - Schuppe-Koistinen I
AD  - Chemical Biology, Science for Life Laboratory, Uppsala, Sweden.
FAU - Bonnefont-Rousselot, Dominique
AU  - Bonnefont-Rousselot D
AD  - Department of Biochemistry, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
FAU - Hainque, Bernard
AU  - Hainque B
AD  - Department of Biochemistry, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
FAU - Imbert-Bismut, Francoise
AU  - Imbert-Bismut F
AD  - Department of Biochemistry, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
FAU - Merz, Michael
AU  - Merz M
AD  - Department of Clinical Pharmacology and Toxicology, University Hospital Zurich,
      University of Zurich, Zurich, Switzerland.
AD  - Mechanistic Safety, Novartis Global Drug Development, Basel, Switzerland.
FAU - Kullak-Ublick, Gerd
AU  - Kullak-Ublick G
AD  - Department of Clinical Pharmacology and Toxicology, University Hospital Zurich,
      University of Zurich, Zurich, Switzerland.
AD  - Mechanistic Safety, Novartis Global Drug Development, Basel, Switzerland.
FAU - Andrade, Raul
AU  - Andrade R
AD  - Unidad de Gestion Clinica de Aparato Digestivo, Instituto de Investigacion
      Biomedica de Malaga, Hospital Universitario Virgen de la Victoria, Universidad de
      Malaga, Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y
      Digestivas, Malaga, Spain.
FAU - van Boemmel, Florian
AU  - van Boemmel F
AD  - Clinic for Hepatology and Rheumatology, Hepatology Section, University Hospital
      Leipzig, Leipzig, Germany.
FAU - Schott, Eckart
AU  - Schott E
AD  - Clinic for Hepatology and Rheumatology, Hepatology Section, University Hospital
      Charite, Berlin, Germany.
FAU - Poynard, Thierry
AU  - Poynard T
AUID- ORCID: http://orcid.org/0000-0002-3726-7230
AD  - Department of Hepatology, Groupe Hospitalier Pitie-Salpetriere, Assistance
      Publique Hopitaux de Paris, Paris, France.
AD  - University Pierre et Marie Curie, Institut National de la Sante et de la
      Recherche Medicale UMR 938, Paris, France.
CN  - Drug Induced Liver Injury- Groupe Hospitalier Pitie-Salpetriere
CN  - Drug Induced Liver Group of the Injury Safer and Faster Evidence-based
      Translation consortium
LA  - eng
PT  - Journal Article
DEP - 20171229
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
EDAT- 2017/12/30 06:00
MHDA- 2017/12/30 06:00
CRDT- 2017/12/30 06:00
PHST- 2017/10/11 00:00 [received]
PHST- 2017/11/26 00:00 [accepted]
PHST- 2017/12/30 06:00 [entrez]
PHST- 2017/12/30 06:00 [pubmed]
PHST- 2017/12/30 06:00 [medline]
AID - 10.1371/journal.pone.0189436 [doi]
AID - PONE-D-17-36532 [pii]
PST - epublish
SO  - PLoS One. 2017 Dec 29;12(12):e0189436. doi: 10.1371/journal.pone.0189436.
      eCollection 2017.